The use of iodine as an aerial disinfectant has been advocated at least since 1926, and experiments on the disinfection of air have been carried out, mainly during World War II. Aerial disinfection of air-raid shelters with iodine vapors as a prophylactic measure against influenza has been recommended. A "relatively tolerable" concentration of 0.1 mg/ft.sup.3 (3.5 ng/ml) was found to be sufficient for a rapid kill of freshly sprayed salivary organisms.
Although it is a strong skin irritant, iodine can be used effectively in medicine as a disinfectant when combined with suitable carriers or complexing agents, e.g., an iodophor. For example, complexed or "tamed iodine" is used in medicine in disinfecting skin (e.g., preoperative preparation of the skin, the surgical disinfection of hands, the disinfection of the perineum prior to delivery, and disinfection of skin prior to transfusions). Iodine preparations are also used for therapeutic purposes, e.g. the treatment of infected and burned skin. Iodine has also been used for the disinfection of medical equipment, such as catgut, catheters, knife blades, ampoules, plastic items, rubber goods, brushes, multiple-dose vials, and thermometers.
Iodine is also known to be useful in disinfecting drinking water. Iodine can inactivate viruses more completely over a wide range of water quality than other halogens. In the presence of organic and inorganic nitrogenous substances, iodine is the cytocide of choice because it takes part in fewer side reactions that consume the disinfectant before it can act. See, e.g., Gottardi, W., Iodine and Iodine Compounds in Disinfection, Sterilization, and Preservation, (Block, Seymour S., Ed.) Lea & Febiger, Philadelphia (3d ed. 1983) and references cited therein.
Johansson, U.S. Pat. No. 4,010,259, described methods and materials for complexing iodine with various iodophors. The iodophors of the '259 patent are described as those in which the iodine is non-covalently bonded to a hydrophilic organic carrier. The organic carrier is insoluble in water, but capable of swelling in water to form a gel. The media of the '259 patent have low capacity for iodine uptake, and iodination occurs slowly. To offset those shortcomings, the '259 patent teaches that iodination is best effected at elevated temperatures.
More recently, Shanbrom reported that suitably constituted iodophors can be used with some success to disinfect platelet-bearing fluid. See, e.g., Shanbrom, E., U.S. Pat. No. 5,360,605, "Preservation of Blood, Tissues and Biological Fluids", which is a continuation in part of the patent application that matured into U.S. Pat No. 5,370,869, "Antimicrobial Preservation of Platelets and Blood Factors", both of which are incorporated herein by reference. Those patents teach that iodine complexed with polyvinyl pyrrolidone ("PVP", e.g., povidone USP), is an effective iodophor for killing or inactivating certain pathogens in biological fluids, particularly platelet-bearing fluid.
The '869 patent teaches that disinfecting agents such as I.sub.2 and hydrogen peroxide (H.sub.2 O.sub.2) can be effectively complexed with polyvinyl pyrrolidone (e.g., povidone USP); and that such PVP complexes can be used to disinfect platelet-containing fluids. The '869 patent teaches that the disclosed PVP disinfecting agents must utilize low molecular weight PVP (povidones), i.e., under 40,000 daltons, preferably under 20,000 daltons. According to the '869 patent, low molecular weight PVP is necessary to avoid the destruction of cells and various blood factors normally occasioned by treatment with iodine.
The '869 patent describes compounding the iodine-complexed low molecular weight povidone into a solution containing 0.1-10% (by weight) povidone. The '869 patent teaches that povidone-I.sub.2 is constituted such that the ratio of povidone to I.sub.2 (povidone:I.sub.2) is at least about 12:1, preferably in the range of 15:1 to 60:1. The '869 patent states that such povidone-,I.sub.2 solutions are effective for disinfecting platelet-bearing fluids, and, presumably, for enhancing the storage stability of such fluids.
The related '605 patent teaches that PVP is a particularly advantageous iodine carrier in that it protects cells against lytic agents such as iodine (i.e., exerts a cytophylactic effect); and that to maintain a cytophylactic effect a PVP:I.sub.2 ratio of at least about 15:1 must be maintained. Even so, the '605 patent teaches that it is still necessary to remove residual iodine from biological fluids treated with povidone-I.sub.2 to avoid the destruction of labile proteins. The '605 patent teaches that this can be effected by removing the iodine (e.g., by adding a competitive iodine-binding material), or by neutralizing the iodine (e.g., by adding a reducing agent such as ascorbic acid, reducing sugars, sodium sulfite, etc.).
Furthermore, povidone is water-soluble and is technically difficult to remove from treated fluids. Crosslinked PVP (XLPVP) an insoluble form of povidone, can also be used as a carrier for iodine (XLPVPI) and is more readily removed from the treated fluid by filtration or centrifugation. However, the flow properties of XLPVPI are poor. Therefore, it is not feasible to use this material in a column or depth filter mode, in which fluids would be passed through a packed bed of the material as needed from large volume processing in a manufacturing-scale setting.
Despite the foregoing, the art has failed to produce an effective, reliable, and commercially practical means for achieving satisfactory levels of disinfection of biological fluids without concomitant destruction of labile proteins. For example, workers have long since struggled to achieve inactivation of viruses that do not possess a lipid envelope (i.e., "non-lipid-enveloped viruses") and similarly hardy pathogens such as viral-elements (e.g., prions). Current methods (e.g., solvent and detergent treatment, methylene blue plus light treatment), inactivate viruses possessing a lipid envelope (i.e., "lipid-enveloped viruses"), but have little or no effect on non-lipid-enveloped viruses or prions. Furthermore, known methods utilizing iodine inactivation fail to effectively control the release of iodine and the duration of exposure of the proteins, and thereby tend to denature proteins.
The methods of the present invention afford a controlled release of iodine into biological fluids so as to achieve selective inactivation of pathogens, especially non-lipid enveloped viruses and viral elements, without simultaneous inactivation or denaturation of valuable but labile proteins in biological fluids. The methods of the present invention afford viral inactivation of biological fluids on a greater scale than that heretofore available.